Y. Lee
Harvard Medical School,
United States
Keywords: sensors, disease detection, diabetes
Summary:
The worsening type-2 diabetes (T2D) epidemic will affect over 600 million people worldwide by 2035. Recently, bariatric surgery has been shown in multiple randomized clinical trials to be superior to traditional pharmaceuticals in managing T2D. Especially, Roux-en-Y gastric bypass (RYGB) is considered as a gold standard with improvements in short-term and long-term metabolic outcomes. However, the risks of surgery along with permanent changes to gastrointestinal anatomy have hampered widespread acceptance. As a less invasive alternative, the duodeno-jejunal endoscopic sleeve was developed to prevent contact between food and duodenal mucosa, and has shown promising results in remitting T2D in patients. However, its pivotal FDA trial was recently halted due to serious complications. There is thus an urgent need for a safe, non-invasive and effective treatment with broad applicability for diabetic patients. In this presentation, we show an orally administered gut-coating formulation that forms a transient physical barrier to nutrient exposure through coating of the luminal surface of proximal intestine, and in essence emulates a critical part of the RYGB non-invasively. Through an in vitro screening study, we identified sucralfate, an orally administrated FDA-approved material, and further engineered sucralfate that can form a thin paste barrier coating on healthy gastrointestinal mucosa. This compound we call it LuCI (Luminal Coating of Intestine) is a powder that can be formulated as a pill and also contains elements that can be imaged using imaging/sensing modalities such as computed tomography (CT) for pharmacokinetics and quality control strategies. Especially, CT imaging analysis revealed that the coating is formed in stomach, duodenum and proximal intestine which mimics the area of RYGB in a reversible manner. The orally administered intestine barrier coater LuCI could transiently reduce the postprandial glucose response acutely and also showed improvements in chronic metabolic outcomes including weight loss, baseline glucose level, fasting insulin level, serum lipid composition and concentrations, and incretin responses (eg, GLP-1). We anticipate that LuCI could be a new therapeutic approach that is safer, associated with significantly less complications, and thus can potentially help a wide T2D patient population.